[Inhibitory effect of all-trans-retinoid and polyphenon-100 on microsatellite instability in a colon cancer line].

Abstract

OBJECTIVE:

To investigate the effects of all-trans-retinoic acid(ATRA) and polyphenon-100 (PP) on genetic instability of human tumor cells via their role in alteration of microsatellite sequence(MS) and the expression of mismatch repair gene hMLH(1) and hMSH(2) in RER(+) (replication error) cells.

METHODS:

RER(+) colon cancer cell line was used as a host for lipofection with pCMV-CAR in which a foreign (CA)(14) repeat was inserted in the coding sequence of LacZ reporter gene, resulting in misreading LacZ frame. Any mutation which made the base number of (CA)(14) tract to be 3-fold resumed normal reading frame of LacZ, and thus led to expression of beta-galactosidase. Variable expression of LacZ in the transfectant cells resulting from RATA or PP treatment was measured by OD reading at lambda 620 after X-gal staining. Expression of mismatch repair genes of hMLH(1) and hMSH(2) was examined at mRNA level by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS:

ATRA at 1 mu mol/L, 0.1 u mol/L and PP at 3 mu g/ml had no significant inhibitory effect on cell proliferation. After being treated with ATRA or PP for 1 week, the blue cells of RKO transfectant clones were significantly reduced, and this meant the mutation of exogenous (CA)(14) in RKO cells were inhibited. But no expression of hMLH(1) and hMSH(2) was observed.

CONCLUSION:

The above data showed both ATRA and PP had inhibitory effects on MS instability of cancer and thus demonstrated directly their beneficial role in stabilization of genomic DNA. However, the present authors have not observed any expression of hMLH(1) and hMSH(2) in RKO cells treated with ATRA or PP.

• Authors: Jian Ye, Hua Lu, Jianwei Zhou, Hanxin Wu, Chenya Wang
• Journal: Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics (Zhonghua Yi Xue Yi Chuan Xue Za Zhi) Vol. 19 Issue 3 Pg. 190-3 (Jun 2002) ISSN: 1003-9406 [Print] China
• PMID: 12048675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Carrier Proteins
• DNA-Binding Proteins
• MLH1 protein, human
• Neoplasm Proteins
• Nuclear Proteins
• Proto-Oncogene Proteins
• RNA, Messenger
• Tretinoin
• Catechin
• MSH2 protein, human
• MutL Protein Homolog 1
• MutS Homolog 2 Protein

Topics

• Adaptor Proteins, Signal Transducing
• Carrier Proteins
• Catechin (pharmacology)
• Cell Division (drug effects)
• Colonic Neoplasms (genetics, pathology)
• DNA-Binding Proteins
• Gene Expression (drug effects)
• Humans
• Lac Operon (genetics)
• Microsatellite Repeats (genetics)
• MutL Protein Homolog 1
• MutS Homolog 2 Protein
• Mutation
• Neoplasm Proteins (genetics)
• Nuclear Proteins
• Plasmids (genetics)
• Proto-Oncogene Proteins (genetics)
• RNA, Messenger (drug effects, genetics, metabolism)
• Transfection
• Tretinoin (pharmacology)
• Tumor Cells, Cultured (drug effects)